The role of 5α-reductase inhibitors in gastro-oesophageal cancer risk: a nested case-control study

Purpose
The strong male predominance of gastro‐oesophageal cancer suggests that sex hormones play an important role. 5α‐Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro‐oesophageal cancer risk.

Methods
We conducted a nested case‐control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use.

Results
The study included 2003 gastro‐oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro‐oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56‐1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50‐0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27‐1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24‐0.99; P value = .046).

Conclusions
We found evidence of reduced gastro‐oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.